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Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis.
Iñigo Gabilondo1, Elena H Martínez-Lapiscina, Eloy Martínez-Heras
1Center of Neuroimmunology and Department of Neurology, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic of Barcelona, Barcelona, Spain.
Annals of Neurology
|October 12, 2013
Summary
Damage to the anterior and posterior visual pathways in multiple sclerosis (MS) indicates trans-synaptic degeneration. This degeneration contributes to chronic axon damage, impacting retinal nerve fiber layer thickness and visual cortex atrophy.
Area of Science:
- Neuroscience
- Ophthalmology
- Radiology
Background:
- Multiple sclerosis (MS) involves demyelination and axonal damage throughout the central nervous system.
- The visual pathway, including the anterior (retina) and posterior (visual cortex) segments, is frequently affected in MS.
- Understanding the pattern of degeneration in the visual pathway is crucial for assessing disease progression and potential therapeutic targets.
Purpose of the Study:
- To investigate the association between damage in the anterior and posterior visual pathways in multiple sclerosis (MS).
- To identify evidence of retrograde and anterograde trans-synaptic degeneration within the visual system of MS patients.
- To correlate retinal nerve fiber layer (RNFL) thickness with structural changes in the posterior visual pathway.
Main Methods:
- A longitudinal study of 100 MS patients over 1 year.
- Retinal optical coherence tomography (OCT) measured anterior visual pathway damage (RNFL thickness, macular volume).
- 3T brain MRI assessed posterior visual pathway damage (visual cortex volumetry/spectroscopy, optic radiation lesion volume), analyzed using Freesurfer and SPM8.
Main Results:
- Voxel-based morphometry (VBM) revealed RNFL thinning associated with visual cortex atrophy and optic radiation lesions at baseline (p < 0.05).
- Visual cortex volume, N-acetyl aspartate levels, and optic radiation lesion volume significantly predicted RNFL thinning, independent of optic neuritis (ON).
- A 1 cm³ decrease in visual cortex volume predicted a 0.6 μm reduction in RNFL thickness; this association persisted at 1-year follow-up.
Conclusions:
- The findings support the presence of trans-synaptic degeneration as a mechanism contributing to chronic axonal damage in MS.
- Atrophy in the visual cortex and lesions in the optic radiations are linked to retinal nerve fiber layer thinning.
- Prior optic neuritis severity correlated with reduced visual cortex volume, suggesting a downstream impact of initial inflammatory events.
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